Disease relevance of Myxoma

• In the autosomal dominant syndrome Carney complex, intracardiac myxomas arise in the setting of lentiginosis and other lesions associated with cutaneous hyperpigmentation, extracardiac myxomas, and nonmyxomatous tumors [1].
• Paraffin-embedded tissue samples from 17 patients with atrial myxoma were investigated for HSV-1 antigen by immunohistochemistry and viral genomic DNA by nested polymerase chain reaction [2].
• Consistent with the observation that infection of CCR5-expressing cells is blocked by herbimycin A and the Jak 2 inhibitor, tyrophostin AG490, we infer that viral infectivity may be dependent on non-G-protein-coupled signal transduction pathways triggered by the infecting myxoma virus particle [3].
• We suggest that atrial myxoma should be added the list of neoplastic and inflammatory diseases predisposing to AA amyloidosis [4].
• Genetic and histologic studies of somatomammotropic pituitary tumors in patients with the "complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas" (Carney complex) [5].

High impact information on Myxoma

• Analysis of additional cases revealed the same mutation in a sporadic case of CNC, and different mutations in three other families, including one with isolated inherited cardiac myxomas [6].
• Encoding of a homolog of the IFN-gamma receptor by myxoma virus [7].
• Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier [8].
• Although cardiac tumorigenesis may require a second somatic mutation, DNA and protein analyses of an atrial myxoma resected from a Carney complex patient with a PRKAR1alpha deletion revealed that the myxoma cells retain both the wild-type and the mutant PRKAR1alpha alleles and that wild-type R1alpha protein is stably expressed [9].
• M-T7 is a secreted myxoma viral immunomodulatory glycoprotein that functions both as a species-specific inhibitor of rabbit IFN-gamma and as a chemokine-binding protein, interacting with a wide range of C, C-C, and C-X-C chemokines in a species-nonspecific fashion [10].

Chemical compound and disease context of Myxoma

• Case 1. Aggressive angiomyxoma of the pelvis: response to luteinizing hormone-releasing hormone agonist [11].
• Inhibition of plasmin, urokinase, tissue plasminogen activator, and C1S by a myxoma virus serine proteinase inhibitor [12].
• Moreover, in cells that are non-permissive for myxoma virus infection, we provide evidence that myxoma virus fails to invoke this tyrosine phosphorylation cascade [3].
• Myxoma virus T2 protein, a tumor necrosis factor (TNF) receptor homolog, is secreted as a monomer and dimer that each bind rabbit TNFalpha, but the dimer is a more potent TNF inhibitor [13].
• The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines [14].

Biological context of Myxoma

• Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by cardiac and extracardiac myxomas in the setting of spotty skin pigmentation and endocrinopathy [15].
• Although we did not observe cardiac myxomas or altered pigmentation in prkar1a(+/-) mice, we did observe some phenotypes similar to CNC, including altered heart rate variability [15].
• In this report we demonstrate that activation of multiple intracellular tyrosine phosphorylation events rapidly ensues following virus adsorption to NIH 3T3.CD4.CCR5 cells and affects the ultimate level of myxoma virus replication [3].
• The myxoma virus T2 (M-T2) gene expresses a secreted protein that contains significant sequence similarity to the ligand binding domains of the cellular tumor necrosis factor (TNF) receptors, specifically inhibits the cytolytic activity of rabbit TNFalpha and is an important virulence factor for myxoma virus infection in rabbits [13].
• Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor homolog, mediate extracellular TNF binding and intracellular apoptosis inhibition [16].

Anatomical context of Myxoma

• Calretinin was found in myxoma cells of all 17 cases but Ki67 was present only in smooth muscle cells or infiltrating cells in some cases. p53 was not detectable in any myxoma [2].
• The myxoma cell line, but not normal fibroblasts, stained for SYN and NCAM [17].
• Symptoms of mitral valve obstruction, the first arm of the classic triad of myxoma presentation, were present in 75 patients (67%), with mostly cardiac failure or malaise [18].
• The myxoma virus tumor necrosis factor (TNF) receptor homolog, M-T2, is expressed both as a secreted glycoprotein that inhibits the cytolytic activity of rabbit TNF-alpha and as an endoglycosidase H-sensitive intracellular species that prevents myxoma virus-infected CD4+ T lymphocytes from undergoing apoptosis [16].
• Although HMGIC also has been implicated in the pathobiology of aggressive angiomyxoma of the vulva, the molecular mechanisms pertaining to this neoplasm are unclear [19].

Gene context of Myxoma

• Molecular and immunohistochemical investigation of protein kinase a regulatory subunit type 1A (PRKAR1A) in odontogenic myxomas [20].
• Calretinin expression has been recently demonstrated in cardiac myxoma, although this finding has not been yet validated [21].
• An abundant mucopolysaccharidic matrix exists, including mucin, within cardiac myxoma [22].
• Thrombomodulin and calretinin may be important diagnostic aids for cardiac myxoma [21].
• All myxomas were negative for c-kit [21].

Analytical, diagnostic and therapeutic context of Myxoma

• U87 and U251 orthotopic xenograft models were used to assess myxoma virus efficacy in vivo [23].
• Reverse transcriptase-polymerase chain reaction demonstrated that increased MMP activity was due, at least in part, to increased transcription and that TIMP-2 transcripts increased in embolic myxomas [24].
• Detergent lysates prepared from myxoma virus-infected cell cultures contained a virally encoded sialyltransferase activity that catalyzed the transfer of sialic acid (Sia) from CMP-Sia to an asialofetuin glycoprotein acceptor [25].
• In addition, inducible binding of M11L to the mitochondrially localized Bax is detected in myxoma virus-infected cells and in M11L/Bax-cotransfected cells as measured by immunoprecipitation and tandem affinity purification analysis, respectively [26].
• MR scans with gadolinium were sometimes helpful when the differential diagnosis included synovitis, Morton's neuroma or intramuscular myxoma, and when it was important to differentiate cystic from solid lesions [27].

References